It is known to calibrate the mass to charge ratio scale of a mass spectrometer by fitting data from known ion peaks (reference standard) to the underlying scan law employed by the mass spectrometer (e.g. time of flight function). This calibration may be performed before, after and/or during the acquisition of an unknown analyte.
Internal calibration refers generally to a calibration method wherein a known reference standard is added to the analyte sample itself and the mixture of analyte sample and reference standard is then ionised and mass analysed. This method can be problematic since the reference standard needs to be carefully selected such that when the reference standard is ionised then reference standard ions are generated at a similar intensity to those of the unknown analyte in order to minimise or avoid saturation effects. Furthermore, the reference standard ions must have mass to charge ratios which are different to the analyte ions in order to avoid interference effects.
Another more common form of calibration is known and is referred to as external calibration or lock massing. External calibration or lock massing refers to a method wherein the calibration is corrected at predetermined calibration time points. This approach relies on the stability of the system between calibration time points. However, this can be problematic if short term perturbations occur to the components of the mass spectrometer (e.g. voltage drift). Furthermore, external calibration or lock massing also suffers from the problem that it increases the cost of the overall mass spectrometer as the approach requires the provision of a separate dedicated ionisation source to generate the reference standard or lockmass ions. Furthermore, the system needs to temporarily switch between the analyte and the reference standard thereby causing a loss of analyte data. A yet further problem with known external calibration methods is that the mass spectrometer will switch to perform a calibration check during an acquisition at predetermined times and this can sometimes accidentally coincide with a time when analyte of interest elute from e.g. a liquid chromatography separation device with the result that at least some potential analyte ions of interest are not generated or detected.
US 2002/130259 (Anderson) discloses a method of calibration in Fourier Transform Ion Cyclotron Resonance mass spectrometry. An embodiment comprises identifying a plurality of ions having known mass differences and having differing charge states, and adjusting the calibration parameters to cause the plurality of ions to be shifted to a relative position that corresponds to the known mass differences. Then measured mass to charge signal of analyte ions are adjusted using the adjusted calibration parameter.
EP 1672673 (Palo Alto) discloses a calibration method in which transformation parameters, A and B, determined using plural peaks of observed mass, are used to transform a measured mass spectrum according to Ax+B, where x is the measured mass. The intercept B can be estimated using mass measurements of a singly charged ion and a doubly charged ion.
It is therefore desired to provide an improved method of calibrating a mass spectrometer.